For research use only. Not for therapeutic Use.
L-Moses (L-45) dihydrochloride is the first potent, selective, and cell-active p300/CBP-associated factor (PCAF) bromodomain (Brd) inhibitor with a Kd of 126 nM[1].
L-Moses (L-45) disrupts PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co-crystal structure of L-Moses with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. A structure using highly homologous (64 % identity) Brd from Plasmodium falciparum, PfGCN5, of which L-Moses is also a potent ligand (isothermal titration calorimetry (ITC) KD 280 nM), is successfully obtained (PDB: 5TPX). L-Moses binds in the acetylated lysines (KAc) -binding pocket of PfGCN (blue ribbon and sticks) and makes H-bonds (dotted lines) through the triazole to N1436 and the first of a network of four water molecules (red spheres)[1].
L-Moses (L-45) shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell-permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use[1].
| Catalog Number | I046284 |
| Synonyms | (1S,2S)-1-N,1-N-dimethyl-2-N-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)-1-phenylpropane-1,2-diamine;dihydrochloride |
| Molecular Formula | C21H26Cl2N6 |
| Purity | ≥95% |
| InChI | InChI=1S/C21H24N6.2ClH/c1-14(19(26(3)4)16-10-6-5-7-11-16)22-20-17-12-8-9-13-18(17)21-24-23-15(2)27(21)25-20;;/h5-14,19H,1-4H3,(H,22,25);2*1H/t14-,19+;;/m0../s1 |
| InChIKey | PCQCTBXCEBIRAC-YRRRDGBXSA-N |
| SMILES | CC1=NN=C2N1N=C(C3=CC=CC=C32)NC(C)C(C4=CC=CC=C4)N(C)C.Cl.Cl |
| Reference | [1]. Moustakim M, et al. Discovery of a PCAF Bromodomain Chemical Probe. Angew Chem Int Ed Engl. 2017 Jan 16;56(3):827-831. |
